Action Points

Note that this phase II trial demonstrated that, among patients with multiple sclerosis, autologous stem-cell transplant was associated with fewer new MS lesions than traditional mitoxantrone.

Be aware that the study was underpowered to look at certain key clinical endpoints such as progression to disability.

Multiple sclerosis (MS) patients who had autologous hematopoietic stem-cell transplantation had significantly fewer new lesions on MRI than those on mitoxantrone, Italian researchers found.

In a randomized, controlled trial, CD34-positive hematopoietic cell transplant reduced the number of new T2 lesions by 79% compared with mitoxantrone over a 4-year study period (P=0.00016), Giovanni Mancardi, MD, of the University of Genova in Italy, and colleagues reported in Neurology.

The therapy also reduced gadolinium-enhancing lesions and annualized relapse rate, but there was no difference in progression of disability, although the study was not powered to look at the latter finding, the researchers noted.

"More research is needed with larger numbers of patients who are randomized to receive either the stem-cell transplant or an approved therapy, but it's very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that are not responding well to standard treatments," Mancardi said in a statement.

The ASTIMS study enrolled 21 patients from seven centers in Italy and Spain from 2004 to 2009 who had relapsing-remitting or secondary progressive MS. They were randomized to intensive immunosuppression followed by either mitoxantrone or autologous hematopoietic stem-cell transplantation every month for 6 months.

The mean age at transplantation was 35.5 years, and the median Expanded Disability Status Scale (EDSS) score at baseline was 6.

ASTIMS was designed as a phase III study, but became a phase II trial with a primary laboratory endpoint -- the cumulative number of new T2 lesions 4 years after randomization -- "when it was clear that the number of enrolled patients was lower than expected," the researchers wrote.

Overall, Mancardi and colleagues found fewer T2 lesions in the stem-cell group than in the mitoxantrone group during follow-up at a median of 2.5 lesions versus a median of eight lesions (rate ratio 0.21, 95% CI 0.10-0.48, P=0.00016).

This effect was evident in the first year and was sustained through 4 years of follow-up, they reported. It was also maintained in all sensitivity analyses.

It also resulted in complete suppression of active inflammatory lesions as measured by gadolinium-enhancing lesions, with no stem-cell patients having new lesions compared with 56% of those on mitoxantrone (P=0.029).

However, there was no significant difference in terms of progression of disability between groups, occurring in 48% of the mitoxantrone group and 57% of the stem-cell group, with no differences in EDSS changes at any point, the researchers said.

Mancardi and colleagues attributed this to the study being underpowered to look for this outcome.

In addition to this limitation, and the fact that the study was changed from phase III to phase II, it was also limited by its small number of cases and by a lack of data on quality of life and brain atrophy outcomes.

In an accompanying editorial, Paolo Muraro, MD, PhD, of Imperial College London, agreed that the lack of improvement in progression of disability was likely due to the study being underpowered.

Muraro also noted that mitoxantrone might not be the contemporary choice of comparator "having lost traction because of its cardiac toxicity and risk of lymphoma," although it was the most appropriate control treatment at the time the trial was started.

Given that stem-cell transplant isn't a licensed therapy for MS, more work is needed, Muraro said, noting that a phase III trial currently underway is likely to gain traction because the current study will "raise interest and catalyze activities to move forward with the new trial."

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